Submissions for variant NM_032043.3(BRIP1):c.2800T>G (p.Phe934Val)

gnomAD frequency: 0.00001  dbSNP: rs863224801

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000200748	SCV000255161	uncertain significance	Familial cancer of breast; Fanconi anemia complementation group J	2022-11-01	criteria provided, single submitter	clinical testing	This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 934 of the BRIP1 protein (p.Phe934Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 216793). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRIP1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Counsyl	RCV000408962	SCV000490107	uncertain significance	Fanconi anemia complementation group J	2016-11-09	criteria provided, single submitter	clinical testing
Counsyl	RCV000410527	SCV000490108	uncertain significance	Ovarian neoplasm	2016-11-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000567218	SCV000666192	likely benign	Hereditary cancer-predisposing syndrome	2023-11-16	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health	RCV000567218	SCV001347583	uncertain significance	Hereditary cancer-predisposing syndrome	2019-08-15	criteria provided, single submitter	clinical testing	This missense variant replaces phenylalanine with valine at codon 934 of the BRIP1 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/31392 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Myriad Genetics, Inc.	RCV003316114	SCV004019383	uncertain significance	Familial cancer of breast	2023-02-28	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics	RCV003316114	SCV004214708	uncertain significance	Familial cancer of breast	2023-10-06	criteria provided, single submitter	clinical testing